CD44v6 as innovative sarcoma target for CAR-redirected CIK cells
| Autor: | V. Leuci, M. Casucci, G. Grignani, R. Rotolo, U. Rossotti, E. Vigna, L. Gammaitoni, G. Mesiano, E. Fiorino, C. Donini, A. Pisacane, L. D. ambrosio, Y. Pignochino, M. Aglietta, A. Bondanza, D. Sangiolo |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | OncoImmunology, Vol 7, Iss 5 (2018) |
| Druh dokumentu: | article |
| ISSN: | 2162-402X 2162402X |
| DOI: | 10.1080/2162402X.2017.1423167 |
| Popis: | Purpose of our study was to explore a new immunotherapy for high grade soft tissue sarcomas (STS) based on cytokine-induced killer cells (CIK) redirected with a chimeric antigen receptor (CAR) against the tumor-promoting antigen CD44v6. We aimed at generating bipotential killers, combining the CAR specificity with the intrinsic tumor-killing ability of CIK cells (CAR+.CIK). We set a patient-derived experimental platform. CAR+.CIK were generated by transduction of CIK precursors with a lentiviral vector encoding for anti-CD44v6-CAR. CAR+.CIK were characterized and assessed in vitro against multiple histotypes of patient-derived STS. The anti-sarcoma activity of CAR+.CIK was confirmed in a STS xenograft model. CD44v6 was expressed by 40% (11/27) of patient-derived STS. CAR+.CIK were efficiently expanded from patients (n = 12) and killed multiple histotypes of STS (including autologous targets, n = 4). The killing activity was significantly higher compared with unmodified CIK, especially at low effector/target (E/T) ratios: 98% vs 82% (E/T = 10:1) and 68% vs 26% (1:4), (p |
| Databáze: | Directory of Open Access Journals |
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